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PHOTACs Enable Optical Control of Protein Degradation

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Targeted Protein Degradation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2365))

Abstract

Proteolysis Targeting Chimeras (PROTACs) are a promising technology to degrade specific target proteins. As bifunctional small molecules, PROTACs induce the ternary complex formation between an E3 ligase and a protein of interest (POI), leading to polyubiquitylation and subsequent proteasomal degradation of the protein in a catalytic fashion. We have developed a strategy to control PROTACs with the spatiotemporal precision of light, which led to light-activated versions, termed PHOTACs (PHOtochemically TArgeted Chimeras). By incorporating an azobenzene photoswitch into the PROTAC, we can reversibly control degradation of the POI, as demonstrated for BRD2-4 and FKBP12. Here, we describe our modular approach and the application of PHOTACs for the optical control of protein levels in detail. PHOTACs hold promise as both research tools and precision pharmaceutics.

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Author information

Authors and Affiliations

  1. Department of Chemistry, New York University, New York, NY, USA

    Martin Reynders & Dirk Trauner

  2. Department of Chemistry, Ludwig Maximilians University of Munich, Munich, Germany

    Martin Reynders

  3. Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA

    Dirk Trauner

  4. NYU Neuroscience Institute, New York University School of Medicine, New York, NY, USA

    Dirk Trauner

Authors
  1. Martin Reynders
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  2. Dirk Trauner
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Correspondence to Dirk Trauner .

Editor information

Editors and Affiliations

  1. Platform Biology, Arvinas, Inc., New Haven, CT, USA

    Angela M. Cacace

  2. Platform Biology, Arvinas, Inc., New Haven, CT, USA

    Christopher M. Hickey

  3. Platform Biology, Arvinas, Inc., New Haven, CT, USA

    Miklós Békés

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Reynders, M., Trauner, D. (2021). PHOTACs Enable Optical Control of Protein Degradation . In: Cacace, A.M., Hickey, C.M., Békés, M. (eds) Targeted Protein Degradation. Methods in Molecular Biology, vol 2365. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1665-9_17

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  • DOI: https://doi.org/10.1007/978-1-0716-1665-9_17

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1664-2

  • Online ISBN: 978-1-0716-1665-9

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